Trifluoperazine inhibition of calmodulin-sensitive Ca 2+-ATPase and calmodulin insensitive (Na + + K +)- and Mg 2+-ATPase activities of human and rat red blood cells

Abstract

Trifluoperazine dihydrochloride-induced inhibition of calmodulin-activated Ca 2+-ATPase and calmodulin-insensitive (Na + + K +)- and Mg 2+-ATPase activities of rat and human red cell lysates and their isolated membranes was studied. Trifluoperazine inhibited both calmodulin-sensitive and calmodulin-insensitive ATPase activities in these systems. The concentration of trifluoperazine required to produce 50% inhibition of calmodulin-sensitive Ca 2+-ATPase was found to be slightly lower than that required to produce the same level of inhibition of other ATPase activities. Drug concentrations which inhibited calmodulin-sensitive ATPase completely, produced significant reduction in calmodulin-insensitive ATPases as well. The data presented in this report suggest that trifluoperazine is slightly selective towards calmodulin-sensitive Ca 2+-ATPase but that it is also capable of inhibiting calmodulin-insensitive (Na + + K +)-ATPase and Mg 2+-ATPase activities of red cells at relatively low concentrations. Thus the action of the drug is not due entirely to its interaction with calmodulin-mediated processes, and trifluoperazine cannot be assumed to be a selective inhibitor of calmodulin interactions under all circumstances.